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34  structures 195  species 0  interactions 1187  sequences 86  architectures

Family: ICAM_N (PF03921)

Summary: Intercellular adhesion molecule (ICAM), N-terminal domain

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This is the Wikipedia entry entitled "Intercellular adhesion molecule". More...

Intercellular adhesion molecule Edit Wikipedia article


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Intercellular adhesion molecule (ICAM), N-terminal domain Provide feedback

ICAMs normally functions to promote intercellular adhesion and signalling. However, The N-terminal domain of the receptor binds to the rhinovirus 'canyon' surrounding the icosahedral 5-fold axes, during the viral attachment process [1]. This family is a family that is part of the Ig superfamily and is therefore related to the family ig (PF00047).

Literature references

  1. Kolatkar PR, Bella J, Olson NH, Bator CM, Baker TS, Rossmann MG; , EMBO J 1999;18:6249-6259.: Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. PUBMED:10562537 EPMC:10562537

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013768

Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) are part of the immunoglobulin superfamily. They are important in inflammation, immune responses and in intracellular signalling events [ PUBMED:9151947 ]. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11/CD18 during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma, due to activation and proteolysis mechanisms at cell surfaces.

ICAM-1 (CD54) contains five Ig-like domains. It is expressed on leucocytes, endothelial and epithelial cells, and is upregulated in response to bacterial invasion. The protein is a ligand for lymphocyte-function associated (LFA) antigens and also a receptor for CD11a,b/CD18, fibrinogen, human rhinovirus and Plasmodium falciparum-infected erythrocytes. ICAM-1 binding sites for CD11a/CD18 and its other binding partners are located in the first domain and are overlapping. ICAM-1 domain 2 seems to play an important role in maintaining the conformation of domain 1 and particularly the structural integrity of the LFA-1 ligand-binding site [ PUBMED:10998349 ].

The 3-dimensional atomic structure of the tandem N-terminal Ig-like domains (D1 and D2) of ICAM-1 has been determined to 2.2A resolution and fitted into a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex [ PUBMED:9539703 ]. Extensive charge interactions between ICAM-1 and human rhinovirusesare largely conserved in major and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is mediated by a divalent cation bound to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid residue on ICAMs.

ICAM-2 (CD102) has two Ig-like domains. It is expressed on endothelial cells, leucocytes and platelets, and binds to CD11a'b/CD18. The protein is refractory to proinflammatory cytokines, and plays an important role in the adhesion of leucocytes to the uninduced endothelium [ PUBMED:10352278 ].

ICAM-3 (CD50) contains five Ig-like domains and binds to leucocyte integrins CD11a'd/CD18. The protein plays an important role in the immune response and perhaps in signal transduction [ PUBMED:10725740 ].

ICAM-4 (LW blood group Ag) is red blood cell (RBC) specific and binds to CD11a'b/CD18. It is associated with the RBC Rh antigens and could be important in retaining immature red cells in the bone marrow, or in the uptake of senescent cells into the spleen [ PUBMED:10846180 ].

ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the telencephalon of the brain. The role of this CD11a/CD18 binding molecule is not yet known [ PUBMED:10741396 ].

VCAM-1 was first described as a cytokine-inducible endothelial adhesion molecule. It can bind to leucocyte integrin VL-4 (very late antigen-4) to recruit leucocytes to sites of inflammation [ PUBMED:11133225 ]. The predominant form of VCAM-1 in vivo has an N-terminal extracellular region comprising seven Ig-like domains [ PUBMED:7531291 ]. A conserved integrin-binding motif has been identified in domains 1 and 4, variants of which are present in the N-terminal domain of all members of the integrin-binding subgroup of the immunoglobulin superfamily. The structure of a VLA-4-binding fragment comprising the first two domains of VCAM-1 has been determined to 1.8A resolution. The integrin-binding motif is exposed and forms the N-terminal region of the loop between beta-strands C and D of domain 1 [ PUBMED:7531291 ]. VCAM-1 domains 1 and 2 are structurally similar to ICAM-1 and ICAM-2 [ PUBMED:11133225 ].

This entry represents the N-terminal domain of ICAM proteins such as ICAM-2, ICAM-3 and ICAM-4.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Ig (CL0011), which has the following description:

Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions. The superfamily can be divided into discrete structural sets, by the presence or absence of beta-strands in the structure and the length of the domains [1]. Proteins containing domains of the C1 and V-sets are mostly molecules of the vertebrate immune system. Proteins of the C2-set are mainly lymphocyte antigens, this differs from the composition of the C2-set as originally proposed [1]. The I-set is intermediate in structure between the C1 and V-sets and is found widely in cell surface proteins as well as intracellular muscle proteins.

The clan contains the following 34 members:

Adeno_E3_CR1 Adhes-Ig_like bCoV_NS7A bCoV_NS8 C1-set C2-set C2-set_2 CD4-extracel DUF1968 Herpes_gE Herpes_gI Herpes_glycop_D I-set ICAM_N ig Ig_2 Ig_3 Ig_4 Ig_5 Ig_6 Ig_7 Ig_C17orf99 Ig_C19orf38 Ig_Tie2_1 Izumo-Ig K1 Marek_A ObR_Ig PTCRA Receptor_2B4 UL141 V-set V-set_2 V-set_CD47


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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: DOMO:DM01682;
Previous IDs: ICAM_N-terminal;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 5
Number in full: 1187
Average length of the domain: 90.1 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 19.08 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 91
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ICAM_N domain has been found. There are 34 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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